Since the original observations that catecholamines are localized within neurons of the central nervous system, there has been considerable effort to associate certain behavioral functions with specific catecholamine neurons. An important rationale of these studies has been to use drugs such as amphetamine to modify both the function of catecholamine containing neurons as well as behavior and to make correlations between the effects. The mechanism of action of amphetamine is not fully understood but the net result of its action is the release of catecholamines from presynaptic sites. The release of norepinephrine, dopamine and 5-hydroxytryptamine from various regions of isolated rat brain has been characterized. Studies with norepinephrine indicate that low concentrations of amphetamine enter the neuron by the neuronal uptake process and displace norepinephrine from intraneuronal binding sites. Using very sensitive methods the release of endogenous amines from isolated brain tissue was measured. Amphetamine is more potent in releasing norepinephrine from isolated cerebral cortex than in releasing dopamine from the same tissue. However, at high concentrations of amphetamine, greater amounts of dopamine are released. These results suggest that there is a selectivity of amphetamine for norepinephrine neurons of cerebral cortex. This selectivity may be conferred by the neuronal uptake of amphetamine into norepinephrine neurons.